DESCRIPTION: The overall objective of this application is to define the functional role of protein kinase C (PKC) isoenzymes in TPA-induced transactivation of the ornithine decarboxylase (ODC) gene, and in TPA-induced tumor promotion in mouse epidermis. The principal investigator hypothesizes that PKC isoforms (, (1 and ( exhibit functional differences in TPA signals to ODC gene expression and tumor promotion, and that this functional divergence of PKC isozymes is the result of differences in the activation of the PKC downstream protein kinase MAPK. To test this hypothesis, the following aims will be carried out. Aim 1. A difference in the role of PKC isoforms in TPA-induced ODC transcription and tumor promotion will be evaluated both by overexpression of the individual isoforms, as well as by attenuation of their activity by expression of dominant negative mutants, using two model systems: (a) the mouse epidermal promotion sensitive cell line (JB6 P+) in vitro; (b) intact mouse skin in vivo, using transgenic mice in which expression of a particular PKC isoenzyme.